Among persons with HIV (PWH), higher alcohol use and having hepatitis C virus (HCV) are separately associated with increased morbidity and mortality. We investigated whether the association between ...alcohol use and mortality among PWH is modified by HCV. Data were combined from European and North American cohorts of adult PWH who started antiretroviral therapy (ART). Self‐reported alcohol use data, collected in diverse ways between cohorts, were converted to grams/day. Eligible PWH started ART during 2001–2017 and were followed from ART initiation for mortality. Interactions between the associations of baseline alcohol use (0, 0.1–20.0, >20.0 g/day) and HCV status were assessed using multivariable Cox models. Of 58,769 PWH, 29,711 (51%), 23,974 (41%) and 5084 (9%) self‐reported alcohol use of 0 g/day, 0.1–20.0 g/day, and > 20.0 g/day, respectively, and 4799 (8%) had HCV at baseline. There were 844 deaths in 37,729 person‐years and 2755 deaths in 443,121 person‐years among those with and without HCV, respectively. Among PWH without HCV, adjusted hazard ratios (aHRs) for mortality were 1.18 (95% CI: 1.08–1.29) for 0.0 g/day and 1.84 (1.62–2.09) for >20.0 g/day compared with 0.1–20.0 g/day. This J‐shaped pattern was absent among those with HCV: aHRs were 1.00 (0.86–1.17) for 0.0 g/day and 1.64 (1.33–2.02) for >20.0 g/day compared with 0.1–20.0 g/day (interaction p < .001). Among PWH without HCV, mortality was higher in both non‐drinkers and heavy drinkers compared with moderate alcohol drinkers. Among those with HCV, mortality was higher in heavy drinkers but not non‐drinkers, potentially due to differing reasons for not drinking (e.g. illness) between those with and without HCV.
To assess the in vitro effect of select antimicrobials on the growth of
and its pharmacodynamic parameters.
Time-kill assays were performed on two reference
strains (ceftriaxone-resistant WHO X and ...ceftriaxone-susceptible WHO F) and one clinical
strain (ceftriaxone-susceptible CS03307). Time-kill curves were constructed for each strain by measuring bacterial growth rates at doubling antimicrobial concentrations of ceftriaxone, ertapenem, fosfomycin and gentamicin. Inputs from these curves were used to estimate minimal bacterial growth rates at high antimicrobial concentrations (
), maximum bacterial growth rates in the absence of antimicrobials (
), pharmacodynamic minimum inhibitory concentrations (zMIC), and Hill's coefficients (κ).
Ceftriaxone, ertapenem and fosfomycin showed gradual death overtime at higher antimicrobial concentrations with a relatively high
, demonstrating time-dependent activity. Compared to WHO F, the
for WHO X was significantly increased, reflecting decreased killing activity for ceftriaxone, ertapenem and fosfomycin. At high ceftriaxone concentrations, WHO X was still efficiently killed. CS03307 also showed a high
for ceftriaxone in spite of a low MIC and no difference in
for fosfomycin in spite of significant MIC and zMIC differences. Gentamicin showed rapid killing for all three strains at high concentrations, demonstrating concentration-dependent activity.
Based on time-kill assays, high-dosage ceftriaxone could be used to treat
strains with MIC above breakpoint, with gentamicin as a potential alternative. Whether ertapenem or fosfomycin would be effective to treat strains with a high MIC to ceftriaxone is questionable.
Introduction
The HIV and hepatitis B virus (HBV) epidemics are interconnected with shared routes of transmission and specific antiviral drugs that are effective against both viruses. Nearly, 300 ...million people around the world live with chronic HBV, many of whom are from priority populations who could benefit from HIV prevention services. Oral pre‐exposure prophylaxis (PrEP) for HIV has implications in the prevention and treatment of HBV infection, but many people at increased risk of HIV acquisition may instead prefer long‐acting formulations of PrEP, which are currently not active against HBV.
Discussion
People at increased risk for HIV acquisition may also be at risk for or already be living with HBV infection. Oral PrEP with tenofovir is effective in preventing both HIV and HBV, and tenofovir is also the recommended treatment for chronic HBV infection. Although implementation of oral PrEP has been challenging in sub‐Saharan Africa, investments in its scale‐up could secondarily reduce the clinical impact of HBV. Long‐acting PrEP, including injectable medicines and implantable rings, may overcome some of the implementation challenges associated with oral PrEP, such as daily pill burden, adherence challenges and stigma; however, current formulations of long‐acting PrEP do not have activity against HBV replication. Ideally, PrEP programmes would offer both oral and long‐acting formulations with HBV screening to optimize HIV prevention services and HBV prevention and care, when appropriate. People who are not immune to HBV would benefit from being vaccinated against HBV before initiating long‐acting PrEP. People who remain non‐immune to HBV despite vaccination may benefit from being offered oral, tenofovir‐based PrEP given its potential for HBV PrEP. People using PrEP and living with HBV who are not linked to dedicated HBV care would also benefit from laboratory monitoring at PrEP sites to ensure safety when using and after stopping tenofovir. PrEP programmes are ideal venues to offer HBV screening, HBV vaccination for people who are non‐immune and treatment with tenofovir‐based PrEP for people with indications for HBV therapy.
Conclusions
Long‐acting PrEP holds promise for reducing HIV incidence, but its implications for the HBV epidemic, particularly in sub‐Saharan Africa, should not be overlooked.
Abstract
Background
In hospital settings, restriction of selected classes of antibiotics is usually believed to contribute to containment of resistance development. We performed a systematic review ...and meta-analysis to assess the effect of restricting the use of specific antibiotic classes on the prevalence of resistant bacterial pathogens.
Methods
We conducted a systematic literature search in Embase and PubMed/OVID MEDLINE. We included studies until June 4, 2020 in which a restrictive antibiotic policy was applied and prevalence of resistance and use of antibiotics were reported. We calculated the overall effect of antimicrobial resistance between postintervention versus preintervention periods using pooled odds ratios (ORs) from a mixed-effects model. We stratified meta-analysis by antibiotic-pathogen combinations. We assessed heterogeneity between studies using the I2 statistic and sources of heterogeneity using meta-regression.
Results
We included 15 individual studies with an overall low quality of evidence. In meta-analysis, significant reductions in resistance were only observed with nonfermenters after restricting fluoroquinolones (OR = 0.77, 95% confidence interval CI = 0.62–0.97) and piperacillin-tazobactam (OR = 0.81, 95% CI = 0.72–0.92). High degrees of heterogeneity were observed with studies restricting carbapenem (Enterobacterales, I2 = 70.8%; nonfermenters, I2 = 81.9%), third-generation cephalosporins (nonfermenters, I2 = 63.3%), and fluoroquiolones (nonfermenters, I2 = 64.0%). Results were comparable when excluding studies with fewer than 50 bacteria. There was no evidence of publication bias for any of the antibiotic-pathogen combinations.
Conclusions
We could not confirm that restricting carbapenems or third-generation cephalosporins leads to decrease in prevalence of antibiotic resistance among Enterobacterales, nonfermenters, or Gram-positive bacteria in hospitalized patients. Nevertheless, reducing fluoroquinolone and piperacilline-tazobactam use may decrease resistance in nonfermenters.
Restriction of selected classes of antibiotics might be useful when specifically targeting a decrease in resistance of nonfermenters. For the remaining selected antibiotic-pathogen combinations, the available evidence is insufficient to conclude that a restrictive antibiotic prescribing policy decreases bacterial resistance.
ObjectivesIt has been suggested that ethnic minorities have been disproportionally affected by the COVID-19. We aimed to determine whether prevalence and correlates of past SARS-CoV-2 exposure varied ...between six ethnic groups in Amsterdam, the Netherlands.Design, setting, participantsParticipants aged 25–79 years enrolled in the Healthy Life in an Urban Setting population-based prospective cohort (n=16 889) were randomly selected within ethnic groups and invited to participate in a cross-sectional COVID-19 seroprevalence substudy.Outcome measuresWe tested participants for SARS-CoV-2-specific antibodies and collected information on SARS-CoV-2 exposures. We estimated prevalence and correlates of SARS-CoV-2 exposure within ethnic groups using survey-weighted logistic regression adjusting for age, sex and calendar time.ResultsBetween 24 June and 9 October 2020, we included 2497 participants. Adjusted SARS-CoV-2 seroprevalence was comparable between ethnic Dutch (24/498; 5.1%, 95% CI 2.8% to 7.4%), South-Asian Surinamese (22/451; 4.9%, 95% CI 2.2% to 7.7%), African Surinamese (22/400; 8.3%, 95% CI 3.1% to 13.6%), Turkish (30/408; 7.9%, 95% CI 4.4% to 11.4%) and Moroccan (32/391; 7.2%, 95% CI 4.2% to 10.1%) participants, but higher among Ghanaians (95/327; 26.3%, 95% CI 18.5% to 34.0%). 57.1% of SARS-CoV-2-positive participants did not suspect or were unsure of being infected, which was lowest in African Surinamese (18.2%) and highest in Ghanaians (90.5%). Correlates of SARS-CoV-2 exposure varied across ethnic groups, while the most common correlate was having a household member suspected of infection. In Ghanaians, seropositivity was associated with older age, larger household sizes, living with small children, leaving home to work and attending religious services.ConclusionsNo remarkable differences in SARS-CoV-2 seroprevalence were observed between the largest ethnic groups in Amsterdam after the first wave of infections. The higher infection seroprevalence observed among Ghanaians, which passed mostly unnoticed, warrants wider prevention efforts and opportunities for non-symptom-based testing.
Introduction
Daily and event‐driven oral pre‐exposure prophylaxis (PrEP) reduce the risk of HIV acquisition. PrEP use can vary over time, yet little is known about the trajectories of PrEP use ...irrespective of the chosen PrEP regimens among men who have sex with men (MSM).
Methods
Using data from a mobile, web‐based diary application collected daily from 17 August 2015 until 6 May 2018, we analysed PrEP use and sexual behaviour in two large cohorts, AMPrEP (Amsterdam, the Netherlands) and Be‐PrEP‐ared (Antwerp, Belgium). In both cohorts, participants could choose between daily and event‐driven oral PrEP every 3 months. We used group‐based trajectory modelling to identify trajectories of PrEP use over time and their determinants. In addition, we estimated the incidence rate of chlamydia, gonorrhoea and syphilis within these trajectories.
Results
We included 516 MSM (n = 322 AMPrEP; n = 194 Be‐PrEP‐ared), of whom 24% chose event‐driven PrEP at PrEP initiation. Participants contributed 225,015 days of follow‐up (median = 508 days IQR = 429−511). Four distinct PrEP use trajectories were identified: ≤2 tablets per week (“low frequency,” 12% of the total population), 4 tablets per week (“variable,” 17%), “almost daily” (31%) and “always daily” (41%). Compared to participants with “low frequency” PrEP use, participants with “variable” (odds ratio OR = 2.18, 95% confidence interval CI = 1.04−4.60) and “almost daily” PrEP use were more often AMPrEP participants (OR = 2.64, 95% CI = 1.27−5.49). “Almost daily” PrEP users were more often employed (OR = 6.76, 95% CI = 2.10−21.75) and were younger compared to participants with “low frequency” PrEP use. In addition, the number of days on which anal sex occurred was lower among participants with “low frequency” PrEP use compared to the other groups (all p<0.001). Compared to “low frequency” PrEP users, the incidence rates of chlamydia and gonorrhoea were higher for participants with “almost daily” and “always daily” PrEP use.
Conclusions
We uncovered four distinct PrEP use trajectories, pointing to different patterns of PrEP use in practice beyond the two‐regimen dichotomy. These trajectories were related to sexual behaviour and rates of sexually transmitted infection. Tailoring PrEP care according to different PrEP use patterns could be an important strategy to improve efficient PrEP delivery.
Surveillance data in high-income countries have reported more frequent SARS-CoV-2 diagnoses in ethnic minority groups. We examined the cumulative incidence of SARS-CoV-2 and its determinants in six ...ethnic groups in Amsterdam, the Netherlands.
We analysed participants enrolled in the population-based HELIUS cohort, who were tested for SARS-CoV-2-specific antibodies and answered COVID-19-related questions between June 24-October 9, 2020 (after the first wave) and November 23, 2020-March 31, 2021 (during the second wave). We modelled SARS-CoV-2 incidence from January 1, 2020-March 31, 2021 using Markov models adjusted for age and sex. We compared incidence between ethnic groups over time and identified determinants of incident infection within ethnic groups.
2,497 participants were tested after the first wave; 2,083 (83·4%) were tested during the second wave. Median age at first visit was 54 years (interquartile range=44–61); 56·6% were female. Compared to Dutch-origin participants (15·9%), cumulative SARS-CoV-2 incidence was higher in participants of South-Asian Surinamese (25·0%; adjusted hazard ratio aHR=1·66; 95%CI=1·16–2·40), African Surinamese (28·9%, aHR=1·97; 95%CI=1·37–2·83), Turkish (37·0%; aHR=2·67; 95%CI=1·89–3·78), Moroccan (41·9%; aHR=3·13; 95%CI=2·22–4·42), and Ghanaian (64·6%; aHR=6·00; 95%CI=4·33–8·30) origin. Compared to those of Dutch origin, differences in incidence became wider during the second versus first wave for all ethnic minority groups (all p-values for interaction<0·05), except Ghanaians. Having household members with suspected SARS-CoV-2 infection, larger household size, and low health literacy were common determinants of SARS-CoV-2 incidence across groups.
SARS-CoV-2 incidence was higher in the largest ethnic minority groups of Amsterdam, particularly during the second wave. Prevention measures, including vaccination, should be encouraged in these groups.
ZonMw, Public Health Service of Amsterdam, Dutch Heart Foundation, European Union, European Fund for the Integration of non-EU immigrants.
Optimising HIV pre-exposure prophylaxis (PrEP) provision requires insight into preferences of PrEP regimens and PrEP discontinuation. We assessed regimen switching and discontinuation and their ...determinants among men who have sex with men (MSM) participating in the Amsterdam PrEP demonstration project.
Between 3-August-2015 and 31-May-2016, we enrolled MSM (n = 374) and TGP (n = 2) in a prospective, longitudinal study. Participants could choose between daily or event-driven PrEP regimens at enrolment and every 3 months. We assessed transition intensities (TI) and determinants of switching (i) between regimens, and (ii) from either regimen to discontinuing PrEP using a multi-state Markov model. PrEP discontinuation was defined as formally stopping study participation or having no study visit for ≥6 months.
Of 367 analysed participants, 73·3% chose daily and 26·7% event-driven PrEP at enrolment. Median follow-up was 3·1 years (IQR 2·9–3·2). 121 participants switched their PrEP regimen at least once (cumulative probability 34·2%, 95% CI 29·4–39·6), with 90 switches from event-driven to daily PrEP (TI 0·35/PY, 95% CI 0·29–0·44) and 113 switches from daily to event-driven PrEP (TI 0·16/PY, 95% CI 0·13–0·20). Switching from event-driven to daily PrEP was associated with younger age, not reporting sex with HIV-positive partners, chemsex, and sexual compulsivity. Switching from daily to event-driven PrEP were associated with younger age and lower sexual satisfaction. 67 participants discontinued PrEP (cumulative probability 17·7%, 95% CI 14·1–22·2), with no difference between regimens: event-driven (n = 23, TI 0·08/PY, 95% CI 0·05–0·13) and daily PrEP (n = 44, TI 0·06/PY, 95% CI 0·04–0·08). Discontinuing daily PrEP was associated with younger age, fewer casual partners, and higher number of condomless anal sex acts with casual partners.
Switching between PrEP regimens was common, while going from event-driven to daily PrEP use was associated with certain sexual-related determinants (i.e. chemsex, sexual compulsivity, no known HIV-positive partners). PrEP discontinuation rates were low and independent of regimens. PrEP care should consider the reasons for choice and switch of regimen and involve education on safely switching or discontinuing PrEP, especially among younger MSM.
ZonMw, H-TEAM, RIVM, GGD research funds, Aidsfonds, Amsterdam Diner Foundation, Gilead Sciences, Gilead Sciences Europe Ltd, Janssen Pharmaceuticals, MAC AIDS Fund, ViiV Healthcare.
As highly effective therapy against hepatitis C virus (HCV) infection is available with rapid uptake, there is newfound optimism for HCV elimination. Nevertheless, certain key populations have a high ...risk of HCV reinfection, in particular men who have sex with men (MSM) in Western European countries. Modelling data indicate that HCV elimination will not be feasible without reduction in risk behaviour, thus supporting the need for effective interventions aimed at reducing risk behaviour and preventing reinfections in MSM.
The ICECREAM study is an international, multi-centred, phase 2, 3-arm randomised trial comparing run-in and intervention periods enrolling MSM with a history of a cured or spontaneously cleared HCV infection. Individuals are followed in routine care for 6 months (i.e. run-in period) and then randomly allocated (1:1:1) to one of the following: a tailored, interactive online risk-reduction behavioural intervention, a validated home-based HCV-RNA self-sampling test service using dried blood spots, or a combination of both. After randomisation, individuals are followed every 6 months until 18 months (i.e. intervention period). Interventions are delivered in addition to standard of care. Online questionnaire measuring risk behaviour over the past 6 months is administered at every visit. The primary outcome is the proportion at risk of HCV infection during run-in versus intervention periods assessed by using the HCV-MOSAIC risk score. The risk score consists of six self-reported HCV-related risk behaviours. Secondary outcomes include incidence of HCV reinfection, changes in the individual risk behaviour items and changes in sexual well-being since changes in sexual behaviour may have an impact on sexual experience. Two hundred forty-six MSM aged 18 years or older will be invited to participate.
The ICECREAM study is a trial aimed at establishing interventions that could effectively decrease the incidence of HCV re-infection in MSM with a previous HCV infection. By offering an online behavioural risk-reduction intervention and HCV-RNA self-sampling, both of which are aimed to influence risk behaviour, we are able to provide products to at-risk MSM that could further reduce population-level HCV incidence and ultimately help reach HCV micro-elimination.
ClinicalTrials.gov NCT04156945. Registered on November 8, 2019.
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